Ipilimumab Induction in Patients With Melanoma Brain Metastases Receiving Stereotactic Radiosurgery

Inclusion Criteria:

* Patients with a histologically-confirmed diagnosis of melanoma who have imaging findings suggestive of 1 to 4 brain metastases
* At least one lesion in the brain that is measurable, which is defined as ≥5 x 5mm (Prior craniotomy and surgical resection is allowed, as long as there is at least one remaining measurable lesion in the brain)
* Patients must be candidates for stereotactic radiosurgery (SRS) and planning to undergo SRS
* Patients must be candidates for ipilimumab as determined by the treating physician
* Patients must be neurologically asymptomatic, or very minimally symptomatic, as judged by the treating physicians
* At least 3 weeks has elapsed from any prior therapy, and the patient has recovered from side effects to ≤ grade 1 toxicities per Common Terminology Criteria (CTC) for Adverse Events
* Age \> or = 18 years old
* Performance status of ECOG of 0 or 1 (ECOG is the Eastern Oncology Cooperative Group Scoring system used to quantify cancer patients' general well-being and activities of daily life; scores range from 0 to 5 where 0 is perfect health and 5 is death)
* Adequate organ and marrow function: alanine aminotransferase (ALT ) \< 2.5x's upper limit of normal (ULN) of the institutional normal reference range, aspartate aminotransferase (AST) \< 2.5x's ULN of the institutional normal reference range, Bilirubin \< 1.5x's ULN of the institutional normal reference range, Creatinine \< 2.0 milligrams per deciliter, Platelets \> 50,000 per microliter
* Women of child-bearing potential must agree to use adequate contraception, defined as complete abstinence from intercourse with men or two methods
* Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

* Previous radiotherapy to the lesion(s) of interest, including prior treatment with whole brain radiation therapy (WBRT). Prior treatment with SRS is allowed if the index lesion(s) is in a different, non-contiguous location than the previously treated lesion.
* Patients who have previously received ipilimumab, PD-1 inhibitors or PD-L1 inhibitors are excluded due to the potential of effects on primary outcome
* Patients who require WBRT or surgery at the time of enrollment
* Neurologic symptoms or imaging findings that necessitate the use of steroids on the day of enrollment or in the prior 7 days
* Highly suspicious magnetic resonance imaging (MRI) or cerebrospinal fluid evidence of leptomeningeal metastases, unless all measurable disease is localized and SRS is considered the treatment of choice
* Concurrent treatment with any other anti-neoplastic drug or concurrent participation in another therapeutic clinical trial
* Patients unable to undergo or tolerate MRI scans (presence of cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, history of allergic reaction/hypersensitivity to gadolinium)
* Women who are pregnant or are nursing
* Patients with absolute lymphocyte count of \<500 cells/microliter, who are known to be HIV positive, who have clinically significant active autoimmune disease, or are receiving immunosuppression following solid organ or stem cell transplant