PDCD1 and metastatic melanoma: The approval of effective targeted and immune therapies has significantly improved the prognosis of metastatic melanoma including brain metastases with a median OS for patients with brain metastases of approximately 7 months for anti-CTLA-4 ipilimumab [42], 10 months for anti-PD-1 pembrolizumab or nivolumab [43] and up to 24 months for BRAF and MEK inhibitors [44].