Brain-Directed Stereotactic Radiation Therapy with or without AGulX Gadolinium-Based Nanoparticles for the Treatment of Brain Metastases

Inclusion Criteria

• Participants must have a biopsy proven solid malignancy and at least one intracranial measurable lesion spanning >= 5 mm in maximal unidimensional size and radiographically consistent with or pathologically proven to be a brain metastasis AND meet one of the following additional criteria regarding the primary site or nature of the intracranial disease: * Melanoma with intracranial growth consistent with tumor progression despite immunotherapy * Gastrointestinal primary * HER2 positive breast cancer (subtype assessed using most representative tissue available in opinion of enrolling clinician and/or study principal investigator [PI]) * Cystic metastases * Metastases >= 2 cm in maximal unidimensional size * Locally recurrent metastases after prior stereotactic radiation * Locally recurrent metastases after prior whole brain radiation ** Patients with metastases from melanoma, gastrointestinal (GI) primaries, or HER2+ breast cancer, as well as those with cystic metastases or metastases >= 2 cm in maximal unidimensional size, who have local recurrences after prior brain-directed radiation can only be treated in the strata permitting prior radiation (last two strata above)
• Age >= 18 years at diagnosis of brain metastases
• Estimated glomerular filtration rate of >= 60 mL/min/1.73 m^2
• Karnofsky performance status of at least 70 (i.e. at minimum, “cares for self” but “unable to carry on normal activity or do active work”)
• Estimated survival based on extracranial disease of at least 3 months in the opinion of the enrolling clinician and/or study PI
• Ability to understand and the willingness to sign a written informed consent document
• The effects of AGuIX on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of the therapeutic component of study participation

Exclusion Criteria

• Participants who cannot undergo a brain MRI
• Participants who cannot receive gadolinium
• Participants with widespread, definitive leptomeningeal disease
• Patients requiring radiation to either > 10 targets (if naive to whole brain radiation) or > 20 targets (if whole brain radiation has been given previously) per the discretion of the treating clinician and/or study PI
• Pregnant women are excluded from this study because of the potential deleterious effects of gadolinium on the developing fetus. Because there is an unknown but potential risk for adverse events in nursing infants, women who are breastfeeding are not eligible for this study
• In cohorts who have received prior brain-directed radiation, patients are not eligible for this study if they have active (at the time of protocol screening) brain metastases that require radiation that are in or within 1.0 cm of the brainstem, eyes, optic nerves, or optic chiasm if the juxtaposed organ at risk (i.e. brainstem, eyes, optic nerves, or optic chiasm) has previously received either > 6.0 Gy in a single fraction or, if prior radiation was fractionated, a cumulative dose in 2.0 Gy equivalents, using an alpha/beta ratio of 2, of > 40.0 Gy. In addition, all patients who have had prior brain-directed radiation, regardless of technique/dose/fractionation, are not eligible for the study until written approval is provided by the study/site PI