Cognitive radio (CR) is an important technique for improving spectral efficiency, letting a secondary system operate in a wireless spectrum when the primary system does not make use of it. While it has been widely explored over the past 25 years, many common assumptions are not aligned with the realities of 5G networks. In this paper, we consider the CR problem for the following setup: (i) infrastructure-based systems, where downlink transmissions might occur to receivers whose positions are not, or not exactly, known; (ii) multi-beam antennas at both primary and secondary base stations. We formulate a detailed protocol to determine when secondary transmissions into different beam directions can interfere with primary users at potential locations and create probability-based interference rules. We then analyze the "catastrophic interference" probability and the "missed transmission opportunity" probability, as well as the achievable throughput, as a function of the transmit powers of the primary and secondary base stations and the sensing window of the secondary base station. Results can serve to more realistically assess the spectral efficiency gains in 5G infrastructure-based cognitive systems.