獣 is always read けもの or けだもの in modern Japanese.
けもの
Simply refers to any kind of beast or animal.
けだもの
It's only used for emotionally deprived, unscrupulous, monstrous individuals, like a murderer, rapist or barbarian. It always refers to the actual perpetrator, so for example, you wouldn't call Adolf Hitler a けだもの. Think of Chucky from Child's Play.
野獣{やじゅう}
Also means beast or brute, but it doesn't carry any negative connotation like けだもの.
しし is not used in modern Japanese as 獣, but 獅子{しし} is an outdated form of ライオン.